CHAMPAIGN, Ill. — High cholesterol levels have been associated with breast cancer spreading to other sites in the body, but doctors and researchers don’t know the cause for the link. A new study by University of Illinois researchers found that the culprit is a byproduct of cholesterol metabolism that acts on specific immune cells so that they facilitate the cancer’s spread instead of stopping it.The study, published in the journal Nature Communications, identifies new potential drug targets that could inhibit the creation or actions of the dangerous cholesterol byproduct, a molecule called 27HC.
"Breast cancer impacts roughly 1 in 8 women. We’ve developed fairly good strategies for the initial treatment of the disease, but many women will experience metastatic breast cancer, when the breast cancer has spread to other organs, and at that point we really don’t have effective therapies. We want to find what drives that process and whether we can target that with drugs,” said Erik Nelson , a professor of molecular and integrative physiology who led the study.
Nelson’s group fed mice with breast cancer tumors a diet high in cholesterol. The researchers confirmed that high levels of cholesterol increased tumor growth and metastasis, and that mice treated with cholesterol-lowering drugs called statins had less metastasis. Then they went further, specifically inhibiting the enzyme that makes 27HC during cholesterol metabolism.
“By inhibiting the enzyme that makes 27HC, we found a suppressor effect on breast cancer metastasis. This suggests that a drug treatment targeting this enzyme could be an effective therapeutic,” said Amy Baek, a postdoctoral researcher at Illinois and the first author of the paper. The researchers also saw unusual activity among specific immune cells – certain types of neutrophils and T-cells – at metastatic sites high in 27HC. “Normally, your body’s immune system has the capacity to attack cancer,” Nelson said, “but we found that 27HC works on immune cells to fool them into thinking the cancer is fine. It’s hijacking the immune system to help the cancer spread.” See a video of Nelson describing the study on YouTube.
Because 27HC acts through the immune system, and not on the breast cancer itself, the researchers believe their findings have broad applicability for solid tumors. They performed experiments looking at colon cancer, lung cancer, melanoma and pancreatic cancer, and found that 27HC increased metastasis for all the tumor types, suggesting that a treatment targeting 27HC could be effective across multiple cancer types. The researchers are working to further understand the pathway by which 27HC affects the immune cells. With clinical partners at Carle Foundation Hospital in Urbana, the team is working to establish whether 27HC has the same pathway in human patients as in mice. “We hope to develop small-molecule drugs to inhibit 27HC,” Nelson said. “In the meantime, there are good cholesterol-lowering drugs available on the market: statins. Cancer patients at risk for high cholesterol might want to talk to their doctors about it.” Nelson also is affiliated with the Cancer Center, the division of nutritional sciences and the Carl R. Woese Institute for Genomic Biology at Illinois. The National Institutes of Health and the Susan G. Komen Foundation supported this work.Editor’s notes: To reach Erik Nelson, call 217-244-5477; email firstname.lastname@example.org The paper “The cholesterol metabolite 27 hydroxycholesterol facilitates breast cancer metastasis through its actions on immune cells” is available online
Approximately 100 students, mentors, family, and friends came to the new Cancer Center at Illinois - located at the Beckman Institute - to celebrate the accomplishments of 24 researcHStart students. Guests enjoyed spending time learning about the summer research experience through a poster session and by oral presentations given by the students from the three host sites: the University of Chicago, the University of Illinois at Chicago, and the University of Illinois at Urbana-Champaign. Dr. King Li, the keynote speaker, delivered an inspiring and engaging dialogue about the direction of medicine and cancer research. Each student was celebrated with a certificate of completion and a warm congratulations from the researcHStart program donors, Debra and Ira Cohen.
Pathways is a publication of the Cancer Community at Illinois, University of Illinois at Urbana-Champaign. Each issue highlights the interdisciplinary and translational work being done within the community by faculty, staff, students, and external partners.
The Cancer Community at Illinois' third researcHStart summer program has just begun! Eight high school students from the surrounding Champaign-Urbana area are spending the next eight weeks working on cancer-focused projects. Students will be acquainted with their faculty mentors and projects during the first week, and progress to participating full-time in their respective labs. Over the course of the program, the students will have the opportunity to hear from various faculty members from the University of Illinois at Chicago, University of Chicago, University of Illinois at Urbana-Champaign, and Carle Foundation Hospital and learn about the impact the speakers have made in the field of cancer research. ResearcHStart students particpate in workshops and group discussions about research papers to grow their understanding of scientific research in an academic setting, and prepare them for a successful transition to a university. This year, students will also have the privilege of participating in a volunteer day at the University of Illinois at Chicago IMD Guest House, where they will prepare welcome bags, bake cookies, and write words of encouragement for guests. The program’s final symposium is scheduled for Friday, August 11, and will feature a poster session and presentations. The keynote speaker will be Dr. King Li, dean and chief academic officer of Carle Illinois College of Medicine.
The inaugural Tissue Microenvironment (TiMe) Training Program Symposium, held on Monday, May 15, 2017, was a great success. Each of the TiMe students presented a summary of their research projects, followed by presentations from members of the External Advisory Board: Dr. David Beebe (University of Wisconsin-Madison), Dr. Peter So (MIT), and Dr. Bruce Wheeler (UCSD), and faculty preceptor Kris Kilian (University of Illinois at Urbana-Champaign). We would like to thank all those who participated in the TiMe Poster Competition and congratulate the winners: Grand Prize: Sixian You; Runners-up: Shachi Mittal and Joanne Li. We also thank our primary sponsors: NIH T32 Award T32EB019944, the Cancer Community at Illinois, and the Beckman Institute for making the event a success. Additional thanks goes to the Interdisciplinary Health Sciences Initiative (IHSI), College of Engineering, Carl R. Woese Institute for Genomic Biology, and the Department of Materials Science and Engineering.